February 26, 2010

First large, population-based study to find an association between procedure and survival; findings offer data for women making difficult, personal decision

Contralateral prophylactic mastectomy (CPM), a preventive procedure to remove the unaffected breast in patients with disease in one breast, may only offer a survival benefit to breast cancer patients age 50 and younger, who have early-stage disease and are estrogen receptor (ER) negative, according to researchers at The University of Texas M. D. Anderson Cancer Center.

Published online Feb. 25 in the Journal of the National Cancer Institute, it's the first population-based study to find an association between the procedure and survival in any group of breast cancer patients. The findings should offer evidence to both the women making this often agonizing decision and the physicians responsible for their care.

According to Isabelle Bedrosian, M.D., assistant professor in M. D. Anderson's Department of Surgical Oncology, a growing number of breast cancer patients are opting for the procedure; recent statistics have shown that the rate of CPM in women with stage I-III breast cancer increased by 150 percent from 1998 to 2003 in the United States.

"In our clinic, we've seen a dramatic increase in the number of women requesting CPM, and across the breast cancer community, studies have shown that the utilization of the procedure is skyrocketing," said Bedrosian, the study's co-corresponding author. "Until now, we've counseled these patients on a very important, personal decision in a vacuum. With our study, our goal was to understand the implications of the surgery and who may benefit."

For the retrospective, population-based study, the researchers used the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) registry, the premier population-based cancer registry now representing 26 percent of the country's population, to identify 107,106 breast cancer patients who underwent a mastectomy for treatment, as well as a subset of 8,902 women who had CPM. All of the women were treated for stages I - III breast cancer between 1998 and 2003. Patients were stratified for ER status, stage of disease and age. Breast cancer-specific survival served as the study's primary endpoint.

Rigorous analysis was paramount in the design of the study, said George J. Chang, M.D., assistant professor in M. D. Anderson's Department of Surgical Oncology.

"It was important to take a critical eye and look at all the different ways the data could be misinterpreted to ensure that biases were not impacting our findings," said Chang, the study's co-corresponding author. "Using multi-variable analysis as well as risk stratification, we did our analysis in many different ways - through SEER, comparing the survival of these patients to that of the general population, as well as examining non-cancer related versus cancer-specific survival. All alternative analyses resulted in the same conclusion; we found one group for whom this surgery offers a true survival benefit."

The researchers found a clear survival benefit for a select group of women that represents less than 10 percent of the breast cancer population. Those younger than age 50 with stage I or II cancer with ER negative disease had a survival benefit of 4.8 percent at five years. However, both Bedrosian and Chang expect that future research will show increased survival benefit with longer follow-up in the population, as a patient's likelihood of getting a second breast cancer increases with time.

While the findings should serve as a guideline for breast cancer patients and their physicians to have an informed, medically-based discussion about CPM, they do not determine that CPM is medically inappropriate for all others with the disease, said the researchers.

"Our research found that breast cancer patients over the age of 60 can be reassured that they will not benefit from CPM," said Bedrosian. "However, there are other populations - such as women between the age of 50 and 60 - where the findings about the procedure remain less clear. In addition, for young women with early stage, estrogen receptive positive breast cancer who receive Tamoxifen for only five years, we really do not know whether they would derive a life-long protective effective from a second breast cancer event. Therefore, for some additional breast cancer patients, CPM may very well be a medically-appropriate option."

In addition, the researchers note, the study captured neither family history nor BRCA status; it also did not include DCIS, or stage 0 breast cancer patients.

In addition to Bedrosian and Chang, Chung Yuan Hu in the Department of Surgical Oncology, also authored the all-M. D. Anderson study.